Recent studies indicate that mammalian chromosomes contain discretecis‐acting loci that control replication timing, mitotic condensation, and stability of entire chromosomes. Disruption of the large non‐coding RNA gene ASAR6 results in late replication, an under‐condensed appearance during mitosis, and structural instability of human chromosome 6. Similarly, disruption of the mouse Xist gene in adult somatic cells results in a late replication and instability phenotype on the X chromosome. ASAR6 shares many characteristics with Xist, including random mono‐allelic expression and (...) asynchronous replication timing. Additional “chromosome engineering” studies indicate that certain chromosome rearrangements affecting many different chromosomes display this abnormal replication and instability phenotype. These observations suggest that all mammalian chromosomes contain “inactivation/stability centers” that control proper replication, condensation, and stability of individual chromosomes. Therefore, mammalian chromosomes contain four types ofcis‐acting elements, origins, telomeres, centromeres, and “inactivation/stability centers”, all functioning to ensure proper replication, condensation, segregation, and stability of individual chromosomes. (shrink)

This special issue of the Modern Law Review addresses a range of key issues - conceptual, ethical, political and practical - arising from the regulatory ...

Ē chartographēsē tou anthrōpinou genetikou ylikou anoixe to dromo gia tē diereunēsē tou phainomenou tēs zōēs. Ē katanoēsē tou tropou leitourgias tōn gonidiōn anamenetai oti tha dōsei apantēseis gia ta aitia ekdēlōsēs sēmantikōn astheneiōn alla kai tha prospherei tropous prolēpsēs ē therapeias tous. Enō etsi einai dynatē ē diagnōsē sēmantikōn astheneiōn, eite progennētika eite meta tē gennēsē tou anthrōpou, sto ameso mellon tha einai dynatē ē epharmogē apotelesmatikōn therapeutikōn agōgōn me tēn anaptyxē tēs gonidiakēs therapeias. Ē epistēmonikē euphoria pou synodeuse (...) tis diavevaiōseis kai tis yposcheseis tōn genetistōn metatrapēke euloga se skeptikismo mprosta stous kindynous pou egkymonei ē kakē chrēsē tōn genetikōn diagnōstikōn methodōn. Etsi, ē allē opsē tēs analysēs tou anthrōpinou gonidiōmatos einai ē dēmiourgia mias "genetikēs tautotētas" kai ē synakolouthē dēmiourgia genetika perithōriopoiēmenōn atomōn. Antistoicha, ē dynatotēta progennētikēs ereunas olo kai perissotero genetikōn "meionektēmatōn" prokalei syneirmous peri "poiotikou elenchou" tēs zōēs. To "phantasma" tēs eugonikēs provallei xana. Ston tomo auto epicheireitai o entopismos tōn krisimōn provlēmatōn pou thetoun oi genetikes exetaseis sto dikaio, ē anadeixē tōn krisimōn isorropiōn kai ē symmetochē se mia syzētēsē pou diexagetai diethnōs me oloena kai megalytero endiapheron. (shrink)

For the average person, genetic testing has two very different faces. The rise of genetic testing is often promoted as the democratization of genetics by enabling individuals to gain insights into their unique makeup. At the same time, many have raised concerns that genetic testing and sequencing reveal intensely personal and private information. As these technologies become increasingly available as consumer products, the ethical, legal, and regulatory challenges presented by genomics are ever looming. Assembling multidisciplinary experts, this volume evaluates the (...) different models used to deliver consumer genetics and considers a number of key questions: How should we mediate privacy and other ethical concerns around genetic databases? Does aggregating data from genetic testing turn people into products by commercializing their data? How might this data reduce or exacerbate existing healthcare disparities? Contributing authors also provide guidance on protecting consumer privacy and safety while promoting innovation. (shrink)

Meiotic defects cause abnormal chromosome segregation leading to aneuploidy in mammalian oocytes. Chromosome segregation is particularly error‐prone in human oocytes, but the mechanisms behind such errors remain unclear. To explain the frequent chromosome segregation errors, recent investigations have identified multiple meiotic defects and explained how these defects occur in female meiosis. In particular, we review the causes of cohesin exhaustion, leaky spindle assembly checkpoint (SAC), inherently unstable meiotic spindle, fragmented kinetochores or centromeres, abnormal aurora kinases (AURK), (...) and clinical genetic variants in human oocytes. We mainly focus on meiotic defects in human oocytes, but also refer to the potential defects of female meiosis in mouse models. (shrink)

Graeme Laurie stepped down from the Chair in Medical Jurisprudence at the University of Edinburgh in 2019. This edited collection pays tribute to his extraordinary contributions to the field. Graeme has often spoken about the importance of 'legacy' in academic work and has forged a remarkable intellectual legacy of his own, notably through his work on genetic privacy, human tissue and information governance, and on the regulatory salience of the concept of liminality. The essays in this volume animate the (...) concept of legacy as lens of analysis for the study and practice of medical jurisprudence. In this light, legacy reveals characteristics of both benefit and burden, as both an encumbrance to and facilitator of the development of law, policy and regulation. Overall, the contributions reconcile the ideas of legacy and responsiveness and show that both dimensions are critical to achieve and sustain the health of medical jurisprudence itself as a dynamic, interdisciplinary and policy-engaged field of thinking. (shrink)

The science and technology of genetic testing is rapidly advancing with the consequences that genetic testing may well offer the prospect of being able to detect the onset of future disabilities. Some recent research also indicates that certain behavioural profiles may have a strong genetic basis, such as the determination to succeed and win or the propensity for risk-taking, which may be of interest to third parties. However, as this technology becomes more prevalent there is a danger that the genetic (...) information may be misused by entities such as employers, insurance companies, educational facilities, and finance companies and that people with particular genetic profiles may be discriminated against.This book explores the different types and the potential uses of genetic testing. The book highlights the ethical and legal dilemmas and the challenges arising as a result of emerging and rapidly advancing genetic science. Chapters in the book assess the importance and impact of the US Genetic Information Non-Discrimination Act (GINA) in the employment and health insurance contexts asking whether it is proving to be an effective tool in addressing the issue of genetic discrimination and alleviating individuals' fears of discrimination. The book then goes on to make the case for regulation at the European Union level in order to protect the privacy of genetic information and to prevent the discriminatory use of genetic information in Europe. It considers what can be learnt from the experience of the US in addressing ethical and legal issues as well as the impact that the UN Convention on the Rights of Persons with Disabilities is having on this debate within the EU. (shrink)

Cytogenetic research has had a major impact on the field of reproductive medicine, providing an insight into the frequency of chromosomal abnormalities that occur during gametogenesis, embryonic development and pregnancy. In humans, aneuploidy has been found to be relatively common during fetal life, necessitating prenatal screening of high‐risk pregnancies. Aneuploidy rates are higher still during the preimplantation stage of development. An increasing number of IVF laboratories have attempted to improve pregnancy rates by using preimplantation genetic diagnosis (PGD) to ensure (...) that the embryos transferred to the mother are chromosomally normal. This paper reviews some of the techniques that are key to the detection of aneuploidy in reproductive samples including comparative genomic hybridization (CGH). CGH has provided an unparalleled insight into the nature of chromosome imbalance in human embryos and polar bodies. The clinical application of CGH for the purposes of PGD and the future extensions of the methodology, including DNA microarrays, are discussed. BioEssays 25:289–300, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Successful preimplantation genetic diagnosis to avoid creating a child affected by a genetically-based disorder was reported in 1989. Since then PGD has been used to biopsy and analyze embryos created through in viuo fertilization to avoid transferring to the mother’s uterus an embryo affected by a mutation or chromosomal abnormality associated with serious illness. PGD to avoid serious and early-onset illness in the child-to-be is widely accepted. PGD prevents gestation of an affected embryo and reduces the chance that the parents (...) will be faced with a difficult decision of whether to terminate the pregnancy. More controversial have been PGD to select the sex of the child-to-be for “family balancing”, PGD for mere susceptibility to disease and for late-onset disorders such as Alzheimer diseas, and most controversially, PGD to create a donor child who is Human Leukocyte Antigen (HLA-matched with a preexisting sibling in need of stem cell transplant. (shrink)

ABSTRACT In 1956 the biomedical world was surprised to hear a report that human cells each contained forty six chromosomes, rather than the forty eight count that had been documented since the 1920s. Application of available techniques to culture human cells in vitro, halt their division at metaphase, and disperse chromosomes in an optical plane permitted perception of visual images not seen before. Researchers continued to obtain the preconceived forty eight counts until reeducation with these novel epistemic ‘chromosomes’ (...) convinced them that they could confidently report forty six chromosomes per cell. Within only a few years, and virtually without dissent, the social community of human cytogeneticists agreed upon a shared visual culture of human chromosome count and morphology. The initial forty six count proved not to be an anomaly. A new comparison of historical and ethnomethodological studies has suggested a better understanding of how applied technologies coupled with altered human perceptions established a new science. Human cytogenetics then collaborated with medical genetics to correlate changes in the new human karyotype with disorders of clinical significance. (shrink)

The author describes his introduction to the field of cytogenetics, with his first viewing of himself, cytogenetically, down the microscope, and the progression of human cytogenetics as an area of study up to its modern integration with molecular genetics and computer technology.

In this review, we focus on the evolutionary and biomedical aspects of the architecture of human chromosome 3 (HSA3) by analyzing chromosomal regions that have been conserved during the evolutionary process, compared to those that have been involved in the genomic restructuring of different placental lineages. Given that the organization of human chromosome 3 is derived when compared to the ancestral primate karyotype, and is an autosome that is commonly implicated in human tumour formation, we (...) examined the patterns of change and the genomic consequences that have resulted from its complex evolutionary history. The data show four discrete chromosomal regions that are frequently implicated in chromosomal rearrangements (3p25, 3p22, 3p12 and 3q21). These are rich in repetitive elements and are commonly implicated in structural rearrangements that underpin human genomic disorders and neoplasias. Additional Supporting Information may be found in the online version of this article. BioEssays 30:1126–1137, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

About one in forty babies is born with a recognisable congenital anomaly at birth. Rapid progress is being made in recognising the genetic contribution to these defects. From over 2000 likely single gene malformation syndromes in humans the gene has been isolated or mapped in about 10%. Despite the availability of animal models, the study of malformations in humans continues to reveal novel genes and unpredicted functions for known genes. The importance of the study of clinical malformations to the understanding (...) of embryological development in humans and other organisms is discussed and reviewed. (shrink)

Efforts to improve the means to diagnose and treat human genetic diseases have a long history in biomedical research and medicine. Now, preimplantation genetic diagnosis provides a new way to prevent the transmission of certain types of human genetic diseases to the next generation. It is an alternative to elective termination of pregnancies.PGD is used to test for genetic diseases that are due to defective single genes or abnormal chromosomes within days of fertilization and prior to the establishment (...) of pregnancy. The procedure essentially begins with the biopsy of one or more cells of a cleavage stage or blastocyst stage preimplantation human embryo that has been produced by in vitro fertilization. In certain cases, PGD can be done on polar bodies—discarded by-products of egg formation containing excess chromosomes—of unfertilized eggs. Then, the cell, or a polar body, is placed into a tube for single gene analysis ), or for chromosome analysis by spreading the nucleus of the cell on a microscope slide ). (shrink)

Introduction A Brief Conceptual Framework for Biology PART ONE: UNDERSTANDING NATURE 1. The Antecedents of Scientific Thought Animism, Totemism, and Shamanism The Paleolithic View Mesopotamia Egypt 2. Aristotle and the Greek View of Nature The Science of Animal Biology The Parts of Animals The Classification of Animals The Aristotelian System Basic Questions 3. Those Rational Greeks? Theophrastus and the Science of Botany The Roman Pliny Hippocrates, the Father of Medicine Erasistratus Galen of Pergamum The Greek Miracle 4. The Judeo-Christian Worldview (...) The Bishop of Hippo Scholastic Thought Islamic Science Books on Beasts Antecedents of a Revolution 5. The Revival of Science Andreas Vesalius and the Study of Structure William Harvey and the Study of Function Sir Francis Bacon’s Great Instauration Induction, Hypothesis, Deduction The Very Small--Animalcules Robert Hooke and the Discovery of Cells 6. Figur’d Stones and Plastick Virtue Marine Life on Mountain Tops? Figured Stones of Unknown Creatures Baron Cuvier Quarries of the Paris Basin Catastrophism and Uniformitarianism William Smith and the Geological Column Understanding Nature in 1850 PART TWO: THE GROWTH OF EVOLUTIONARY THOUGHT 7. The Paradigm of Evolution First Questions The Paradigm of Natural Theology First Answers 8. Testing Darwins Hypotheses Have Life Forms Changed over Time? Do Species Evolve into Different Species over Time? Has There Been Time Enough for Evolution? Is Natural Selection the Mechanism of Change? The Genetic Basis of Natural Selection Accounting for the Diversity of Life 9. In the Light of Evolution Comparative Anatomy Embryonic Development Classification Microstructure Molecular Processes 10. Life over Time The Origin of Life The Rise of Multicelled Organisms What Is a Phylum? Burgess Shale Metazoans Early Evolution of the Vertebrates The Age of Dinosaurs Birds, Mammals, and Flowering Plants The Rancho La Brea Tar Pits Human Evolution The Role of Extinction in Evolution PART THREE: CLASSICAL GENETICS 11. Pangenesis What Is the Question? Hippocrates and Aristotle The Darwinian Answer Assembling the Data Formulating the Hypothesis by Induction Galton’s Rabbits 12. The Cell Theory The Discovery of Cells: Robert Hooke Schwann and Cells in Animals Gametes as Cells Omnis cellula e cellula? The Technology of Cell Research 13. The Hypothesis of Chromosomal Continuity The Ephemeral Nucleus Schneider, Flemming, and Cell Division The Chromosomes and inheritance Gamete Formation Fertilization 14. Mendel and the Birth of Genetics Model for Monohybrid Crosses Model for Dihybrid Crosses Mendel’s Laws Initial Opposition to Mendelism 15. Genetics + Cytology: 1900-1910 Sutton’s Model The Cytological Basis of Mendel’s Laws Boveri and Abnormal Chromosome Sets Variations in Mendelian Ratios The Discovery of Sex Chromosomes 16. The Genetics of the Fruit Fly Morgan’s First Hypothesis Morgan’s Second Hypothesis The Fly Room Linkage and Crossing-Over The Cytological Proof of Crossing-Over Mapping the Chromosomes The Final Proof The Determinants of Sex The Conceptual Foundations of Classical Genetics 17. The Structure and Function of Genes One Gene, One Enzyme The Substance of Inheritance The Watson-Crick Model of DNA Genes and the Synthesis of Proteins The Genetic Code PART FOUR: THE ENIGMA OF DEVELOPMENT 18. First Principles The Peripatetic Stagirite The Death and Rebirth of Scientific Thought Harvey and Malpighi A Two-Millennial Summing Up Preformation versus Epigenesis 19. The Century of Discovery Von Baer’s Discovery of the Mammalian Ovum Darwin’s Contribution to Embryology Haeckel and Recapitulation 20. Descriptive Embryology Germ Layers The External Development of the Amphibian Embryo The Internal Development of the Amphibian Embryo 21. The Dawn of Analytical Embryology His, Roux, and Mosaic Development Driesch and Regulative Development Novelty in Development Cell Lineage Nucleus or Cytoplasm? Fin de Siècle 22. Interactions during Development Amphibian Organizers Secondary Organizers The Reacting Tissue The Chemical Nature of the Organizer Putting It All Together Conclusion Further Reading References Illustration Credits Index. (shrink)

This paper calls fresh attention to ethical problems surrounding prenatal testing by focusing on genetic knowledge gained through evolving testing procedures. Advances in reproductive and prenatal genetic testing include non-invasive tests, such as Verifi and Materniti21, designed to gather detailed information regarding fetal DNA as early as 10 weeks. Meanwhile, a new method of chromosomal microarray has proved more reliable than karyotyping in detecting fetal abnormality. This method detects abnormalities in 1 out of every 60 pregnancies in which karyotyping (...) identified the fetus as “normal.” Chromosomal microarray directly compares fetal DNA to DNA from a presumptively “healthy person” to identify genetic deviations. The chromosomal microarray method thus assumes a human genetic blueprint—that is, a normal genotype, deviance from which is risky and open to medical diagnosis. But, according to philosopher and geneticist Jackie Leach Scully, there is no genetic blueprint for human beings. Rather, genetic variation is constant. Thus, notes Scully, genetic discourse could free medical discourse from the dictates of the binary between normal and abnormal, although mistaken belief in a genetic blueprint can foil this alternative way of speaking and thinking. Prenatal testing has received critical philosophical attention from both disability theorists and feminists. Adrienne Asch suggests that prenatal testing and diagnosis stigmatizes already-existing persons with disabilities by suggesting that bodily deviance is intolerable. Licia Carlson coined the phrase “prenatal prototypes” to describe the obfuscating results of genetic profiling carried out on the fetus. The philosophical conversation Asch and Carlson stimulate involves higher stakes now that testing uncovers fetal genotype and reveals mere genetic deviation in order to aid reproductive decision-making. I argue that prenatal testing, and especially the most recently developed testing procedures described above, forecloses Scully’s alternative discourse of genetic variation by supporting an ideal of a singular “healthy genotype,” deviance from which is to be uncovered and avoided. Mobilizing this insight by drawing on the work of feminist disability scholars like Asch and Carlson, I seek to foreground the play between norm and deviance. I expose the normalizing field of statistical risk, operating in excess of medical diagnosis, which requires potential parents to manage and avoid deviance itself. (shrink)

SCL (TAL1/TCL5) is a member of the helix‐loop‐helix family of transcription factors. Originally identified because of its involvement in a tumour‐specific chromosomal translocation, overexpression of the SCL gene is the most common molecular abnormality found in human T cell leukaemia. Transgenic models have now formally demonstrated that overexpression of SCL within the T cell lineage is capable of causing malignant transformation. Gene targeting experiments have revealed that the SCL gene is crucial for the development of primitive haematopoiesis in the (...) mouse and is also required for the generation of all adult haematopoietic lineages. Biochemical studies have indicated some of the proteins which interact with SCL and this has refined the hypotheses concerning the mechanisms by which SCL plays a role in leukaemogenesis and haematopoietic development. (shrink)

A common account sees the human genome sequencing project of the 1990s as a “natural outgrowth” of the deciphering of the double helical structure of DNA in the 1950s. The essay aims to complicate this neat narrative by putting the spotlight on the field of human chromosome research that flourished at the same time as molecular biology. It suggests that we need to consider both endeavors – the human cytogeneticists who collected samples and looked down the (...) microscope and the molecular biologists who probed the molecular mechanisms of gene function – to understand the rise of the human genome sequencing project and the current genomic practices. In particular, it proposes that what has often been described as the “molecularization” of cytogenetics could equally well be viewed as the turn of molecular biologists to human and medical genetics – a field long occupied by cytogeneticists. These considerations also have implications for the archives that are constructed for future historians and policy makers. (shrink)

A common account sees the human genome sequencing project of the 1990s as a “natural outgrowth” of the deciphering of the double helical structure of DNA in the 1950s. The essay aims to complicate this neat narrative by putting the spotlight on the field of human chromosome research that flourished at the same time as molecular biology. It suggests that we need to consider both endeavors – the human cytogeneticists who collected samples and looked down the (...) microscope and the molecular biologists who probed the molecular mechanisms of gene function – to understand the rise of the human genome sequencing project and the current genomic practices. In particular, it proposes that what has often been described as the “molecularization” of cytogenetics could equally well be viewed as the turn of molecular biologists to human and medical genetics – a field long occupied by cytogeneticists. These considerations also have implications for the archives that are constructed for future historians and policy makers. (shrink)

A common account sees the human genome sequencing project of the 1990s as a “natural outgrowth” of the deciphering of the double helical structure of DNA in the 1950s. The essay aims to complicate this neat narrative by putting the spotlight on the field of human chromosome research that flourished at the same time as molecular biology. It suggests that we need to consider both endeavors – the human cytogeneticists who collected samples and looked down the (...) microscope and the molecular biologists who probed the molecular mechanisms of gene function – to understand the rise of the human genome sequencing project and the current genomic practices. In particular, it proposes that what has often been described as the “molecularization” of cytogenetics could equally well be viewed as the turn of molecular biologists to human and medical genetics – a field long occupied by cytogeneticists. These considerations also have implications for the archives that are constructed for future historians and policy makers. (shrink)

This essay presents the early days of human cytogenetics, from the late 1950s until the mid 1970s, as a historical series of images. I propose a chronology moving from photographs of bodies to chromosome sets, to be joined by ultrasound images, which provided a return to bodies, by then focused on the unborn. Images carried ontological significance and, as I will argue, are principal characters in the history of human cytogenetics. Inspired by the historiography of heredity and (...) genetics, studies on visual cultures, the conceptualization of circulation, and the sociology of pregnancy, I suggest that cytogenetics, through its focus on pregnancy, pregnant women, and their offspring, found strategic living materials that stabilized human chromosome studies as a biomedical, post-eugenics practice. The historicity of each path displays a wide circulation of objects, tools, and methods that condensed on images that shared in the centuries-old visual expertise that medicine and botany had manufactured. (shrink)

Alongside the renowned male pioneers of medical cytogenetics, many women participated in investigations at the laboratory bench and the bedside, both in Europe and the Americas. These women were committed to this new biological and clinical practice—cytogenetics, the origins of contemporary genetic diagnosis—and contributed to the creation of new biological concepts and settings centered on the study of chromosome imaging. This paper will review the contributions made by a group of woman scientists from a wide geographical distribution, situating their (...) names and research agendas within the history of a field dating back to early plant and insect cytogenetics. Rather than an exhaustive compendium of women geneticists, this essay presents a kind of historical reconstruction that can be achieved by placing women at center stage in their geographies and networks of circulating cytogenetic knowledge and practices thereby relating a history of genetic images though the work carried out by women, retrieving their agency and constructing an inclusive history of an influential contemporary biomedical practice as it gained increasing influence in the laboratory and the clinic. (shrink)

The second volume in an unprecedented publishing event: the complete College de France lectures of one of the most influential thinkers of the last century Michel Foucault remains among the towering intellectual figures of postmodern philosophy. His works on sexuality, madness, the prison, and medicine are classics his example continues to challenge and inspire. From 1971 until his death in 1984, Foucault gave public lectures at the world-famous College de France. These lectures were seminal events. Attended by thousands, they created (...) benchmarks for contemporary critical inquiry. The lectures comprising Abnormal begin by examining the role of psychiatry in modern criminal justice, and its method of categorizing individuals who "resemble their crime before they commit it." Building on the themes of societal self-defense in the first volume of this series, Foucault shows how and why defining "abnormality" and "normality" were prerogatives of power in the nineteenth century, shaping the institutions--from the prison system to the family--meant to deal in particular with “monstrosity,” whether sexual, phsyical, or spiritual. The College de France lectures add immeasurably to our appreciation of Foucault's thought, and offer a unique window on his singular worldview. (shrink)

Recent work has led to the discovery that two severe hereditary human pathologies are caused by biotin deficiency. Significantly, administration of pharmacologic doses of biotin can provide clinically effective treatment. Both diseases are autosomal recessive in inheritance but differ in their associated enzymatic deficiencies. The clinical, enzymatic, and genetic characteristics of these pathologies are reviewed here.

Hibakusha are “witnesses” of the atomic bombings, not just in a standard sense but also in the instrumental sense. For medical and scientific experts, hibakusha are biological resources of unparalleled scientific value. Over the past seventy years, the hibakusha bodies have narrated what it means to be exposed to radiation. In this paper, I explore studies at the Atomic Bomb Casualty Commission that examined hibakusha bodies as sites where risk could be read. I focus on a period from the mid-1950s (...) to 1975, during which new methods, practices, and technologies allowed ABCC scientists to investigate chromosomes as a way to study radiation exposure and human risk. By focusing on chromosomal aberrations, ABCC scientists connected their work directly to the emerging infrastructure for radiobiology at the time. ABCC administrators actively sought out such prestige, especially given their relationship with the Atomic Energy Commission. The shift in approach would also alleviate some public relations problems with which the institution was struggling. Launching a cytogenetics program required some older practices that had assumed American privilege and dominance to be abandoned. Eventually, the decision to let chromosomes speak of radiation exposure brought about fundamental changes in ABCC, which came to symbolize the model for future studies at the organization, especially as ABCC was transitioning to a US-Japan binational organization. More broadly, this case highlights the intricate scientific negotiation of radiation risk where uncertainties necessarily prevail. (shrink)

In this paper, we hypothesize that X chromosome-associated mechanisms, which affect X-linked genes and are behind the immunological advantage of females, may also affect X-linked microRNAs. The human X chromosome contains 10% of all microRNAs detected so far in the human genome. Although the role of most of them has not yet been described, several X chromosome-located microRNAs have important functions in immunity and cancer. We therefore provide a detailed map of all described microRNAs located (...) on human and mouse X chromosomes, and highlight the ones involved in immune functions and oncogenesis. The unique mode of inheritance of the X chromosome is ultimately the cause of the immune disadvantage of males and the enhanced survival of females following immunological challenges. How these aspects influence X-linked microRNAs will be a challenge for researchers in the coming years, not only from an evolutionary point of view, but also from the perspective of disease etiology. (shrink)

Despite its importance, abnormal interactions between the proximal and distal upper extremity muscles of stroke survivors and their impact on functional task performance has not been well described, due in part to the complexity of upper extremity tasks. In this pilot study, we elucidated proximal–distal interactions and their functional impact on stroke survivors by quantitatively delineating how hand and arm movements affect each other across different phases of functional task performance, and how these interactions are influenced by stroke. Fourteen subjects, (...) including nine chronic stroke survivors and five neurologically-intact subjects participated in an experiment involving transport and release of cylindrical objects between locations requiring distinct proximal kinematics. Distal kinematics of stroke survivors, particularly hand opening, were significantly affected by the proximal kinematics, as the hand aperture decreased and the duration of hand opening increased at the locations that requires shoulder abduction and elbow extension. Cocontraction of the extrinsic hand muscles of stroke survivors significantly increased at these locations, where an increase in the intermuscular coherence between distal and proximal muscles was observed. Proximal kinematics of stroke survivors was also affected by the finger extension, but the cocontraction of their proximal muscles did not significantly increase, suggesting the changes in the proximal kinematics were made voluntarily. Our results showed significant proximal-to-distal interactions between finger extension and elbow extension/shoulder abduction of stroke survivors exist during their functional movements. Increased cocontraction of the hand muscles due to increased neural couplings between the distal and proximal muscles appears to be the underlying mechanism. (shrink)

"This work is designed to be an introduction to abnormal psychology. The problems considered, however, belong equally to normal psychology. The present volume consists of selected lectures (with the exception of four) from courses on abnormal psychology delivered at the Tufts College Medical School (1908-10) and later at the University of California (1910). These again were based on a series of papers on the Unconscious published in the Journal of Abnormal Psychology (1908-9) of which they are elaborations. Since the lectures (...) were delivered a large amount of new material has been incorporated and the subject matter considered in more detail and more exhaustively than was practical before student bodies. The four additional lectures (X, XI, XII and XIII) appeared in abbreviated form in the same Journal (Oct., Nov., 1912) under the title "The Meaning of Ideas as Determined by Unconscious Settings." As the subconscious and its processes are fundamentals both in the structure of personality and in the many mechanisms through which personality, normal and abnormal, finds expression, the first eight lectures are devoted to its exposition. Indeed, the subconscious is not only the most important problem of psychology, it is the problem. The study of its phenomena must be preliminary to that of the functioning mechanisms of both the normal mind and of those special pathological conditions--the psycho-neuroses--which modern investigators are tracing to its perversions. It ought to be possible to construct the theory of the subconscious by inductive methods on the basis of facts of observation just as any theory of the physical sciences is constructed. This task I have set before myself as well as that of giving precision to our conception of the theory and taking it out of the domain of philosophical concepts. With this purpose in view I have endeavored to apply the method of science and construct the theory by induction from the data of observation and experiment. I have divided the subconscious into two classes, namely (1) the unconscious, or neural dispositions and processes, and (2) the coconscious, or actual subconscious ideas which do not enter the content of conscious awareness. In these lectures I have also endeavored (Lectures XIV-XVI) to develop the phenomena of the emotional innate dispositions which I conceive play one of the most fundamental parts in human personality and in determining mental and physiological behavior. Experimental methods and the well-known clinical methods of investigation have been employed by me as far as possible. The data made use of have been derived for the most part from my own observations, though confirmatory observations of others have not been neglected. Although a large number and variety of subjects or cases have been studied, as they have presented themselves in private and hospital practice, the data have been to a large extent sought in intensive studies, on particular subjects, carried on in some cases over a period of many years. These subjects, because of the ease with which subconscious and emotional phenomena were either spontaneously manifested or could be experimentally evoked, were particularly suitable for such studies and fruitful in results. It is by such intensive studies on special subjects, rather than by casual observation of many cases, that I believe the deepest insight into mental processes and mechanisms can be obtained. The favorable reception which was given to the first edition of this work has tempted me in preparing a new edition at the request of the publishers to incorporate four additional chapters dealing with the general principles underlying the structure and dynamic elements of human personality (Lecture XVII) and a study of a special problem in personality in which these principles are involved, namely, the psychogenesis of multiple personality as illustrated by a study of the case known as B.C.A. (Lectures XVIII-XX)." (PsycINFO Database Record (c) 2012 APA, all rights reserved). (shrink)

Small tandem DNA duplications in the range of 15 to 300 base‐pairs play an important role in the aetiology of human disease and contribute to genome diversity. Here, we discuss different proposed mechanisms for their occurrence and argue that this type of structural variation mainly results from mutagenic repair of chromosomal breaks. This hypothesis is supported by both bioinformatical analysis of insertions occurring in the genome of different species and disease alleles, as well as by CRISPR/Cas9‐based experimental data from (...) different model systems. Recent work points to fill‐in synthesis at double‐stranded DNA breaks with complementary sequences, regulated by end‐joining mechanisms, to account for small tandem duplications. We will review the prevalence of small tandem duplications in the population, and we will speculate on the potential sources of DNA damage that could give rise to this mutational signature. With the development of novel algorithms to analyse sequencing data, small tandem duplications are now more frequently detected in the human genome and identified as oncogenic gain‐of‐function mutations. Understanding their origin could lead to optimized treatment regimens to prevent therapy‐induced activation of oncogenes and might expose novel vulnerabilities in cancer. (shrink)

Despite its widespread existence, the adaptive role of aneuploidy (the abnormal state of having an unequal number of different chromosomes) has been a subject of debate. Cellular aneuploidy has been associated with enhanced resistance to stress, whereas on the organismal level it is detrimental to multicellular species. Certain aneuploid karyotypes are deleterious for specific environments, but karyotype diversity in a population potentiates adaptive evolution. To reconcile these paradoxical observations, this review distinguishes the role of aneuploidy in cellular versus organismal evolution. (...) Further, it proposes a population genetics perspective to examine the behavior of aneuploidy on a populational versus individual level. By altering the copy number of a significant portion of the genome, aneuploidy introduces large phenotypic leaps that enable small cell populations to explore a wide phenotypic landscape, from which adaptive traits can be selected. The production of chromosome number variation can be further increased by stress‐ or mutation‐induced chromosomal instability, fueling rapid cellular adaptation. (shrink)

Previous studies have reported abnormal amplitude of low-frequency fluctuation and regional homogeneity in patients with migraine without aura using resting-state functional magnetic resonance imaging. However, how whole brain functional connectivity pattern homogeneity and its corresponding functional connectivity changes in patients with migraine without aura is unknown. In the current study, we employed a recently developed whole brain functional connectivity homogeneity method to identify the voxel-wise changes of functional connectivity patterns in 21 patients with migraine without aura and 21 gender and (...) age matched healthy controls. Moreover, resting-state functional connectivity analysis was used to reveal the changes of corresponding functional connectivities. FcHo analyses identified significantly decreased FcHo values in the posterior cingulate cortex, thalamus, and left anterior insula in patients with migraine without aura compared to healthy controls. Functional connectivity analyses further found decreased functional connectivities between PCC and medial prefrontal cortex, between AI and anterior cingulate cortex, and between THA and left precentral gyrus. The functional connectivities between THA and PCG were negatively correlated with pain intensity. Our findings indicated that whole brain FcHo and connectivity abnormalities of these regions may be associated with functional impairments in pain processing in patients with migraine without aura. (shrink)

In humans over 15% of X‐linked genes have been shown to ‘escape’ from X‐chromosome inactivation (XCI): they continue to be expressed to some extent from the inactive X chromosome. Mono‐allelic expression is anticipated within a cell for genes subject to XCI, but random XCI usually results in expression of both alleles in a cell population. Using a study of allelic expression from cultured lymphoblasts and fibroblasts, many of which showed substantial skewing of XCI, we recently reported that the (...) expression of genes lies on a contiunuum between those that are subject to inactivation, and those that escape. We now review allelic expression studies from mouse, and discuss the variability in escape seen in both humans and mice in genic expression levels, between X chromosomes and between tissues. We also discuss current knowledge of the heterochromatic features, DNA elements and three‐dimensional topology of the inactive X that contribute to the balance of expression from the otherwise inactive X chromosome. (shrink)

At metaphase, DNA in a human chromosome is estimated to be compacted at least 10,000 fold in length.1,2 However, the higher order mechanisms by which the chromosomes are organized in interphase and subsequently further condensed in mitosis have largely remained elusive. One generally overlooked participant in chromosome condensation is DNA replication. Many early studies of eukaryotic chromosome organization and cell fusions have suggested that DNA replication plays a role in chromosome compaction. Recent phenotypic analysis of (...) Drosophila DNA replication mutants has revitalized this old idea. In this review, the role of DNA replication in chromosome condensation will be examined. BioEssays 24:411–418, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The structures of specific chromosome regions, centromeres and telomeres, present a number of puzzles. As functions performed by these regions are ubiquitous and essential, their DNA, proteins and chromatin structure are expected to be conserved. Recent studies of centromeric DNA from human, Drosophila and plant species have demonstrated that a hidden universal centromere‐specific sequence is highly unlikely. The DNA of telomeres is more conserved consisting of a tandemly repeated 6–8 bp Arabidopsis‐like sequence in a majority of organisms as (...) diverse as protozoan, fungi, mammals and plants. However, there are alternatives to short DNA repeats at the ends of chromosomes and for telomere elongation by telomerase. Here we focus on the similarities and diversity that exist among the structural elements, DNA sequences and proteins, that make up terminal domains (telomeres and subtelomeres), and how organisms use these in different ways to fulfil the functions of end‐replication and end‐protection. BioEssays 27:685–697, 2005. © 2005 Wiley Periodicals, Inc. (shrink)